Randomized trial on protein vs carbohydrate in ad libitum fat reduced diet for the treatment of obesity
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International Journal of Obesity (1999) 23, 528±536
ß 1999 Stockton Press All rights reserved 0307±0565/99 $12.00
http://www.stockton-press.co.uk/ijo
Randomized trial on protein vs carbohydrate in
ad libitum fat reduced diet for the treatment of
obesity
AR Skov1, S Toubro1, B Rùnn2, L Holm1 and A Astrup1*
1
Research Department of Human Nutrition, The Royal Veterinary and Agricultural University, Copenhagen, Denmark and 2Department
of Mathematics, The Royal Veterinary and Agricultural University, Copenhagen, Denmark
OBJECTIVE: To study the effect on weight loss in obese subjects by replacement of carbohydrate by protein in ad
libitum consumed fat-reduced diets.
DESIGN: Randomized dietary intervention study over six months comparing two ad libitum fat reduced diets (30% of
total energy) strictly controlled in composition: High-carbohydrate (HC, protein 12% of total energy) or high-protein
(HP, protein 25% of total energy).
SETTING AND PARTICIPANTS: Subjects were 65 healthy, overweight and obese subjects (50 women, 15 men, aged
18 ± 55 y) randomly assigned to HC (n 25), HP (n 25) or a control group (C, n 15). All food was provided by self-
selection in a shop at the department, and compliance to the diet composition was evaluated by urinary nitrogen
excretion.
MAIN OUTCOME MEASURE: Change in body weight, body composition and blood lipids.
RESULTS: More than 90% completed the trial. Weight loss after six months was 5.1 kg in the HC group and 8.9 kg in
the HP group (difference 3.7 kg, 95% con®dence interval (CI)(1.3 ± 6.2 kg) P < 0.001), and fat loss was 4.3 kg and 7.6 kg,
respectively (difference 3.3 kg (1.1 ± 5.5 kg) P < 0.0001), whereas no changes occurred in the control group. More
subjects lost >10 kg in the HP group (35 %) than in the HC group (9 %). The HP diet only decreased fasting plasma
triglycerides and free fatty acids signi®cantly.
CONCLUSIONS: Replacement of some dietary carbohydrate by protein in an ad libitum fat-reduced diet, improves
weight loss and increases the proportion of subjects achieving a clinically relevant weight loss. More freedom to
choose between protein-rich and complex carbohydrate-rich foods may allow obese subjects to choose more lean
meat and dairy products, and hence improve adherence to low-fat diets in weight reduction programs.
Keywords: low-fat diets; ad libitum; high-protein; high-carbohydrate; cardiovascular risk factors; blood lipids; body
composition; obesity
Introduction of potential weight loss and of potential adverse
effects, has never been addressed in long-term inter-
vention studies.
The prevalence of obesity is increasing rapidly in the A number of short-term studies suggest that protein
Western world, and its comorbidities are of major per kJ exerts a more powerful effect on satiety than
concern. To prevent obesity, it is recommended that both carbohydrate and fat.1,3,7 ± 15 If this is also true in
fat should be no more than 30% of the energy intake. the long-term, replacing some of the dietary carbohy-
The background for this advice is that overconsump- drate by protein should improve the weight loss
tion of high-fat foods plays a role in weight gain and obtained by using low-fat diets under ad libitum
obesity in susceptible individuals.1 ± 3 This concept has conditions. In contrast, observational studies have
been used clinically to induce and maintain weight found that dietary protein content is positively asso-
loss in obese subjects by administration of low-fat ciated with body fatness.16 We therefore undertook
diets consumed ad libitum. However, there is some the present study to compare two ad libitum, strictly
debate about the ef®ciency of the low-fat ad libitum controlled, low-fat diets, with respect to changes in
principle, as compared to calorie counting.4 ± 6 A body weight, body composition and blood lipids in
reduction in energy intake can be achieved by a obese subjects over a period of six months.
reduction in dietary fat content, which can induce a
modest weight loss, but the optimal relative propor-
tion of dietary carbohydrate and protein, both in terms
Subjects and methods
*Correspondence: Arne Astrup, Research Department of Human
Nutrition, The Royal Veterinary and Agricultural University,
Rolighedsvej 30, 1958 Frederiksberg C, Copenhagen, Denmark. Subjects
E-mail: ast@kvl.dk
Received 26 August 1998; revised 30 November 1998; accepted Included in the study were 65 overweight and obese
8 January 1999 subjects (25 < body mass index (BMI) < 34 kg=m2)Low-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
529
of both genders, aged 18 ± 56 y, (Table 1). All subjects Approval was obtained from the Municipal Ethical
were volunteers recruited through advertisement or a Committee of Copenhagen and Frederiksberg. The
waiting list. They underwent a brief medical screening study was performed in accordance with the Helsinki
examination, including a medical history, a routine II declaration, and each subject signed an informed
physical examination and blood tests (haemoglobin, consent document before the study commenced.
leucocytes, sodium, potassium, glucose, alkaline
phosphates and electrocardiogram (ECG)) before
Study design
enrollment. In addition to normal screening results,
the subjects all met the criterion of being weight The study was conducted as a dietary intervention for
stable for 2 months before entry. This was con- six months, strictly controlled in terms of macronu-
®rmed by weighing at the department. trient composition. The outcome measures were
The subjects of the intervention group were ran- changes in body weight and composition, proportion
domly assigned to either high-carbohydrate (HC: 25 of subjects achieving a certain weight loss ( >5 kg
subjects) or high-protein (HP: 25 subjects) diet, both and >10 kg), total and intra-abdominal fat mass and
low in fat (30% of total energy) or to a control group changes in the plasma values of total and high density
(C: 15 subjects) (Table 2). To ensure group matching lipoprotein (HDL) cholesterol, triglycerides and free
with respect to BMI, gender, age and smoking habits, fatty acids.
a third party, who did not know the subjects or their
identity, exchanged group membership of six subjects. Diet
Alcohol intake, assessed by 7 d dietary records, was All the food for the intervention groups was provided
equal in the three groups. The subjects in the three by a shop at the Department and could be consumed
groups had similar histories with respect to the course ad libitum. The C group was instructed not to change
of their obesity; of the subjects in the HC, HP and C anything in their dietary habits whilst shopping in
groups, 20%, 28% and 20%, respectively, reported ordinary food shops. The targeted composition of the
that they were overweight at school start (not statis- two diets was: HP: 25% of energy (E%) as protein and
tically signi®cant (NS)), and 16%, 28% and 28% 45 E% as carbohydrate; HC: 12 E% as protein and 58
reported that they were overweight at age 18 y (NS). E% as carbohydrate (See Table 2). A variety of
Self help, public health services and alternative thera- different food items made up an all-round assortment
pies for weight reduction had all been used to a similar offered by the shop and this covered the most
degree in the three groups. common foods. The selection varied seasonally.
Table 1 Physical characteristics of subjects in the two intervention groups and one control groupa
Age Gender Smoking b Body weight Height BMI Body fat
(y) (M/F) (kg) (cm) (kg/m2) (kg)
High-carbohydrate (n 25) 39.4 2.0 6/19 9 (5.7 1.5) 88.6 1.9 169.5 0.0 30.8 0.4 30.5 1.5
High-protein (n 25) 39.8 1.9 6/19 9 (8.0 2.0) 87.0 1.9 170.0 0.0 30.0 0.4 28.5 1.4
Controls (n 15) 37.6 2.2 3/12 5 (9.1 2.4) 88.1 1.8 171.0 0.0 30.3 0.7 29.6 1.8
a
Values are means s.e.m. There were no differences between groups by ANOVA.
b
Number of smokers in group (number of cigarettes smoked per day).
BMI body mass index.
Table 2 Macronutrient composition and energy content in intervention dietsa
High-carbohydrate High-protein
Actual Actual
Targeted b 0 ^ 3 months c 4 ^ 6 months d Targeted b 0 ^ 3 months c 4 ^ 6 months d
Energy from protein (%) 12 12.1 0.1 12.2 0.1 25 24.7 0.1 24.1 0.2
Energy from carbohydrate (%) 58 59.4 0.2 59.0 0.2 45 45.9 0.2 46.8 0.2
Energy from fat (%) 30 28.5 0.2 28.8 0.2 30 29.4 0.2 29.1 0.2
Total energy (MJ/d) - 10.6 0.3** 11.2 0.5** - 8.6 0.4 9.3 0.4
Fiber content (g)e - 22.8 1.6** - 18.6 1.4
Alcohol (g)e - 14.5 3.2 - 14.4 2.7
Energy density (kJ/g)f - 4.9 0.1 5.0 0.1 - 4.7 0.1 5.0 0.2
a
Plus-minus values are means s.e.m.
b
The targeted macronutrient composition according to the protocol.
c
Dietary composition, intake and energy density as registered by the shop computer system during the initial three months of dietary
intervention, calculated as mean daily values.
d
Dietary composition, intake and energy density as registered by the shop computer system during the last three months of dietary
intervention, calculated as mean daily values.
e
Data from 7 d dietary records.
f
Calculated without drinks, on the basis of computer registrations.
**P < 0.001, *P < 0.01 as compared to the corresponding value in the high-protein group.Low-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
530
Protein sources were primarily dairy products and more than 20 g=d. This was controlled by self-report-
meat (beef, pork, poultry, lamb, ®sh and offal). ing of alcohol intake at each visit in the shop.
Carbohydrate sources were primarily vegetables,
fruits, breads, rice and pasta, but chocolate and
simple sugars, in the form of sweets, were also Anthropometric measurements and body composition
available. Body weight was measured weekly, with subjects
The subjects collected their food from the shop wearing light clothing, on a decimal scale (Seca
twice a week. Food items could be chosen freely model 707, Copenhagen, Denmark) in both interven-
within the dietary design and individual `shoppings' tion groups. Subjects in the control group were only
were registered in a computer system designed speci- weighed at baseline and after three and six months.
®cally for the purpose, described in detail pre- Sagittal diameter and waist and hip circumferences
viously.17 At each shop visit, all food items were were measured in all groups at baseline and at the end
selected by the subject and bar code scanned by a of the study. Body composition was determined by a
dietician. This made it possible to monitor achieve- dual energy X-ray absorptiometry (DEXA) scanning
ment of the scheduled macronutrient distribution and, (Hologic 1000=W, Hologic, Inc., Waltham, MA, soft-
if necessary, to modify the selected provisions. Unea- ware version 5.61). Subjects wore only underwear and
ten food and left-overs, weighed to the nearest 1 g, a cotton T-shirt during the scan. For quality control,
were taken into account in the calculation of the spine phantoms were scanned daily.
energy content of the actual selection. We used bar Intra-abdominal adipose tissue was estimated from
codes, unique for each food item, and uncoded infor- DEXA-scans and anthropometry by the equation
mation about energy and macronutrient composition given by Treuth et al:18
of the food item. The information used was provided Intra-abdominal fat area (cm2) 7 208.2
by the database, Dankost1 dietary assessment soft- 4.62(sagittal diameter, cm) 0.75 (age, y) 1.73
ware (National Food agency of Denmark, Sùborg, (waist, cm) 0.78 (trunk fat, %).
Denmark) or by the food manufacturers. The calcu-
lated energy content of the food was not known by the Laboratory analyses
subjects. Venous blood samples were drawn from an antecubi-
Subjects were instructed thoroughly in how to tal vein after an overnight fast. After centrifugation,
prepare the foods, but they could also choose ready- aliquots were stored at 7 20 C, prior to analysis.
prepared dishes. The aim was to fully control the Plasma cholesterol, HDL-cholesterol and triglycerides
dietary composition of the LP and HP subjects' food, were determined enzymatically with a Cobas Mira-
and they were encouraged to collect all their foods, Analyzer (Boehringer Mannheim Gmbh, Mannheim,
including `empty calories' and caloric beverages Germany) and plasma nonesteri®ed fatty acids
(except for alcohol) from the grocery store. Any (NEFA) were determined by an enzymatic colori-
deviation from this principle should be recorded metric method using a Wako NEFA C test kit
analogous to recording of food waste and leftovers. (Wako Chemicals GmbH, Neuss, Germany).
For validation of the food registration method in the
shop the protein intake was monitored by an objective
biological markers, 24 h urinary nitrogen excretion
(24-h UN) each month and the completeness of the Statistical analysis
urine sample was controlled.17 Urine was collected at
baseline and at three months and six months of the
study. A questionnaire investigation was performed Differences between groups in proportion of subjects
after six months of dietary intervention, to asses the achieving a certain weight loss, that is, 5 kg or
impact of the dietary intervention on the quality of 10 kg after three months and six months, respec-
life.18 The questionnaires were structured with mostly tively, were tested by a chi-squared test and the
precoded response categories and a few open ques- difference between intervention groups is expressed
tions. The subjects were asked to rate numerous life as odds-ratio (OR). Group differences in changes in
quality variables relating to the dietary altera- body weight and blood lipids after 0, three months and
tion=intervention. These included physical, social six months of intervention, were analyzed by a mixed
and psychological well-being, acceptability and model for analysis of variance, with interaction
palaltability, and discomforts from different organ between `group' and `time' included as ®xed effects
systems such as nausea, constipation, frequent bowel and `subjects' included as random effect. One chi-
movements, abdominal pain, musculo-skeletal dis- squared test was performed to test for equal baseline
comforts and tiredness. levels of blood lipids in the three groups and another
The subjects were instructed not to change their chi-squared test was made to test for the effect of time
physical activity pattern or smoking habits during the in the control group. Changes in body weight, com-
study. The subjects were also allowed to leave their position and blood lipids are given as expected mean-
alcohol habits unchanged, given that the intake was no s s.e.m. (or 95% con®dence intervals (CI)), with
corresponding P-values estimated under the statisticalLow-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
531
model. Differences between groups in intra-abdom- attractive and tastes as good as `normal' food. To
inal fat area were tested by one-way ANOVA. assess if differences in weight loss may have been
P < 0.05 was considered signi®cant. in¯uenced by palatability and acceptability, we
Life quality variables were tested with nonpara- analyzed the weight loss in sub-groups of both inter-
metric statistics: Chi-squared tests for differences vention groups and found no evidence to support the
between groups in yes=no questions and Kruskal- contention that differences in acceptability affected
Wallis one-way analysis of variance by ranks for weight loss. In addition, no differences were found
group differences with respect to multiple choice with respect to discomforts from different organ
questions (four choices). To account for the multiple systems, such as tiredness=sleeping problems,
comparisons the signi®cance level was set as shortness of breath, abdominal symptoms (rum-
P < 0.01. Statistics Analysis Package, SAS# 6.10 bling=distended stomach, constipation=frequent
(SAS Institute, Cary, NC, USA) and SigmaStat# 1.0 bowel movements, abdominal pain after meal), gen-
(Jandel Scienti®c GmbH, Erkrath, Germany) were eral edema or discomforts in muscles or joints. The
used in the statistical analysis. subjects generally considered the dietary alteration to
be easier to comply with than they had expected.17
Body weight and composition
Results Pre-treatment body weights were similar in all three
groups and no signi®cant change occurred in the
Compliance and acceptability control group (Figure 1) Weight loss after three
Two subjects dropped out of each intervention group, months was greater in the HP group than in the HC
due to change of address or non-compliance, and one group: 7.5 kg vs 5.0 kg (difference 2.5 kg (0.6 ± 4.2 kg)
subject was excluded from the control group, due to P < 0.02). After six months, weight loss was 5.0 kg
elective surgery. A total of 60 subjects completed the (3.6 ± 6.4 kg) in the HC group and 8.7 kg (7.3 ±
trial (92%), 23 in each intervention group and 14 in 11.9 kg) in the HP group (difference 3.7 kg (1.3 ±
the control group. 6.2 kg) P 0.0002). After three months of dietary
Table 2 shows the average daily macronutrient intervention, more subjects had lost 5 kg body
intake, energy intake and energy density in the six weight in the HP group (19=24 (79%)) than in the
intervention months, separated into two three month HC group (12=23 (52%)) (P < 0.05) (Figure 2). After
periods. The achievement of the targeted differences six months, more subjects had lost 10 kg body
in protein intakes in the intervention groups was weight in the HP group (8=23 35%) than in the
supported by the use of 24 h UN as an objective HC group (2=23 9%) (OR 5.6 (1.1 ± 30.2)
marker of protein intake. At baseline, dietary protein P < 0.001). At three months, fat loss was 3.8 kg
intake calculated from 24 h UN was similar in the (2.6 ± 5.0 kg) in the HC group and 5.8 kg (4.6 ±
three groups and did not change in the control group 7.0 kg) in the HP group (difference: 2.0 kg (0.4 ± 3.7)
over the period. However, in the HP group, protein P < 0.02). After six months, fat loss was 4.3 kg (3.1 ±
intake increased from a baseline value of 91.4 g=d
(81.0 ± 101.82) to a six months intervention average of
107.8 g=d (102.2 ± 112.1 g=d) (P < 0.05), while corre-
spondingly, a decrease from 91.1 g=d (82.5 ± 99.7 g=d)
to 70.4 g=d (64.8 ± 76.0 g=d) (P < 0.05) was observed
in the HC group (Group difference: P < 0.0002).
Dietary ®ber intake changed from 17.8 g=d at baseline
to 18.6 g=d in the intervention period in the HP group,
whereas dietary ®ber intake correspondingly changed
in the (HC) group from 16.1 g=d to 22.8 g=d. Hence,
the increase in daily dietary ®ber content was 7 g
lower in the HP group than in the HC group
(P < 0.05). Alcohol intake at baseline was
17.7 3.3 g=d in the (HC) group, 15.0 2.2 g=d in
the HP group and 11.1 3.0 g=d in the C group (NS)
and did not change during dietary intervention.
There were no signi®cant group differences in the
questionnaire responses in any of the measures of Figure 1 Changes in body weight in overweight and obese
appetite or palatability. None of the subjects in either subjects randomized to ad libitum fat-reduced diets: high-carbo-
group responded that they most of the time felt hungry hydrate (protein 12% of total energy; n 25), high-protein (pro-
soon after a meal or felt a bit hungry during the whole tein 25% of total energy; n 25) or to a control group (no
intervention; n 15). Values are means s.e.m. There were no
day. Both in the HP and in the (HC) group, only 4% of differences in baseline values of body weight. Grouptime
the subjects did not agree that low-fat food is as interaction: P < 0.0001.Low-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
532
Figure 4 Changes in intra-abdominal adipose tissue (IAAT)
Figure 2 Proportion of subjects having lost >5 kg or 10 kg body
estimated from dual energy X-ray absorptiometry (DEXA)
weight after three months and six months of dietary interven-
scans and anthropometry by the equation given by Treuth et
tion. Comparisons between groups were made by a chi-squared
al19: IAAT (cm2) 7 208.2 4.62(sagittal diameter, cm) 0.75
test. *P < 0.05 for the comparison of difference with the high-
(age, y) 1.73 (waist, cm) 0.78 (trunk fat, %). * P < 0.0001 for
carbohydrate group.
the comparison of changes between high-protein group and the
two others. Values are means s.e.m.
Figure 3 Changes from baseline in body fat mass in overweight
and obese subjects randomized to two ad libitum fat-reduced
diets, either a high-carbohydrate (protein 12% of total energy;
n 25), or high-protein (protein 25% of total energy; n 25) or a Figure 5 Changes in blood lipids from base-line values in
control group (no intervention; n 15). *P < 0.02 for the compar- overweight and obese subjects randomized to ad libitum fat-
ison between the two intervention groups. **P < 0.0001 for the reduced diets: high-carbohydrate (HC: protein 12% of total
comparison between the two intervention groups. Values are energy; n 25), high-protein (HP: protein 25% of total energy;
means s.e.m. n 25) or to a control group (C: no intervention; n 15). *P < 0.05
and **P < 0.01 for the comparison of change from baseline and
for difference between intervention groups and control group. P
HDL high density lipoproteins.
5.5 kg) in the HC group and 7.6 kg (6.2 ± 9.0 kg) in the
HP group (difference: 3.3 kg (1.1 ± 5.7) P < 0.0001)
(Figure 3). Intra-abdominal adipose tissue decreased
by 33.0 cm2 in the HP group and by 16.8 cm2 in the
seen in the control group during the six months of
HC group (P < 0.0001), whereas it increased in the
intervention (Figure 5). Total cholesterol and HDL-
control group by 15.2 cm2, differing from both inter-
cholesterol decreased in both the HC and HP groups,
vention groups (P < 0.0001) (Figure 4).
with no group differences (Figure 5). Plasma free fatty
acids decreased by approx 30% after six months in the
HP group, while they were unchanged in the HC
Blood lipids group (P < 0.05). In contrast to the increase in
No group differences in baseline values of blood plasma triglycerides after three months in the HC
lipids were found, and no signi®cant changes were group, a decrease by 0.37 mmol=l (0.15 ± 0.59Low-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
533
mmol=l) was found in the HP group (P 0.001). After is unlikely that the provision of free food enhanced
six months, no signi®cant group differences remained weight loss.
(Figure 5). Dietary composition was not monitored as closely
in the C-group as in the intervention groups, since
food was not provided to the control group from the
study shop. However, as we chose experimental
Discussion conditions that were very natural, we do not consider
this will invalidate the status of the C-group as a
reference group.
The present study shows that two diets with a dietary The adherence to the dietary compositions of the
fat content reduced to slightly below 30 E%, cause two intervention groups was high, as assessed by the
clinically relevant weight losses during ad libitum excretion of 24 h UN, which was used as a marker of
consumption, compared to a control diet with a fat protein intake.25 The agreement between the dietary
content of about 40 E%. This study further shows that protein intake, as estimated by the shop computer and
the HP diet induces a larger weight loss than the HC the UN excretion was very high (r 0.84,
diet. After six months intervention, the HP diet P < 0.0001), and the achievement of a two-fold dif-
induced a 3.7 kg (1.3 ± 6.2 kg) larger weight loss, ference in UN excretion between the HP and HC
which was mainly due to a reduction in body fat groups supports that statement that the targeted
mass. Moreover, in the HP group, 35% of the subjects macronutrient compositions of the intervention diets
lost >10 kg, whereas only 9% in the HC group were actually reached.
achieved this goal (OR 5.6 (1.1 ± 30.2)). Both fat- We ®nd it very likely that some unintended volun-
reduced diets decreased the intra-abdominal fat stores, tary energy restriction occurred in both intervention
but the decrease in the HP group was two-fold greater groups, due to the subjects being highly motivated to
than in the HC group. lose weight. This may have enhanced the weight loss
The weight loss on the two ad libitum fat-reduced in the two intervention groups, but is unlikely to have
diets was markedly higher than those previously in¯uenced the weight loss difference between the HP
reported in normal weight subjects2,19 ± 21 and slightly and HC groups.
above the weight losses reported in overweight and The mechanisms responsible for the larger weight
obese subjects.22 There are two likely reasons for this. loss caused by the HP diet than by the HC diet might
Firstly, the small weight losses observed in some of be due to both a reduced energy intake and a greater
the low-fat intervention trials can partly be attributed thermogenic effect of protein.
to low adherence to the low-fat diet composition.23 We found the reported energy intake during the
Most trials using the ad libitum low-fat principle intervention was lower in the HP group than in the
reported so far have instructed the subjects how to HC group by 2 MJ (0.94 ± 3.05 MJ, P < 0.001), which is
make the dietary changes, but have not ensured that more than suf®cient to explain the larger weight loss in
the subjects actually consumed a diet with the pre- the HP group. Rolls et al12 found that high protein and
scribed composition. Adherence to the diet, as high starch foods produced greater satiety than high fat,
assessed by recovered label in expired air in subjects high sucrose or mixed content foods. The lower energy
consuming meals enriched with 13C-glucose under intake in the HP group is in accordance with most meal
free-living conditions, has been shown to be positively test studies, showing a higher satiating effect of protein
related to weight loss.23 In contrast, our shop system, than carbohydrate, when compared joule for
where all foods during six months were free of charge, joule.7,9,12,15,26 A high protein intake also seems to be
allowed a more strict control of macronutrient com- able suppress the following day's energy intake more
position, while allowing the subjects freedom to select than an isoenergetic amount of carbohydrate. Stubbs et
appropriate food items in the shop. Thus the compli- al 27 studied the relationship between carbohydrate and
ance to the two diets as assessed by UN excretion was protein balances and the next day's spontaneous energy
high and 92% of the subjects completed the 6 months intake during a seven-day stay in a respiration chamber,
of treatment. and found that every megajoule of increased protein
We ®nd it very likely that the provision of free stores on day 1 produced a reduction in energy intake on
food during the intervention trial played a role and the subsequent day amounting to 2.1 MJ. For a similar
that the high compliance was also economically increase in carbohydrate stores, the reduction in energy
motivated. However, in a recent study, obese sub- intake was only 0.4 MJ. Thus the more pronounced
jects participated in four different behavioural weight effect of protein than of carbohydrate in inhibition of
control programs that differed only with respect to energy intake found in short-term studies is con®rmed
the way the food was provided to the subjects: no by the present study and shown to be maintained for at
food provision, meal plans, provision of food (paid least six months.
for by the subjects) or food provided free.24 Weight Palatability of the diet has been shown to be an
losses were similar in the three latter groups, but important determinant of energy intake,28 and the
signi®cantly different from that of the group that lower energy intake in the HP group than in the HC
received the behavioural program alone. Therefore, it group could therefore have been due to a lowerLow-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
534
palatability of the HP diet. However, we ®nd this intra-abdominal fat deposition is characterised by
explanation unlikely since no differences were found increased total cholesterol, low density lipoprotein
in palatability between the intervention groups after (LDL)-cholesterol, triglyceride and free fatty acid
six months. Moreover we found that in the question- levels, and decreased HDL levels.35 Hence, the
naire on appetite the subjects' responses to questions larger reduction in the intra-abdominal fat depots in
were independent of their achieved weight loss. the HP group, may be expected to reduce the risk of
Moreover, no differences with respect to physical these comorbidities. Although a bene®cial effect of
well-being were found. The subjects generally consid- weight loss on plasma lipids was found in both
ered the dietary alteration to be easier to comply with intervention groups, more favourable improvements
than they had expected (Holm L, SKov AR, Astrup A. were seen in the HP group (Figure 5). There was a
unpublished results). The results therefore suggest that slight transient increase in plasma triglycerides after
the lower energy intake in the HP diet was due to a three months in the HC group, whereas a reduction
higher satiating effect of protein than of carbohydrate. was seen in the HP group. The increase in plasma
In addition to the effect on energy intake, the HP triglycerides has been reported to occur on isoener-
diet may increase energy expenditure more than the getic low-fat, high carbohydrate diets,22,36, but not
HC diet, as the post-prandial thermogenesis of protein under ad libitum conditions where weight loss is
amounts to 30% of its energy content, whereas that of allowed to occur.22 Moreover, plasma NEFA were
carbohydrate is only 4 ± 8%.29,30 On a daily basis, the reduced only in the HP group. The greater improve-
difference in protein and carbohydrate intakes ment in that cardiovascular risk pro®le after six
between the HP group and the HC group can be months on the HP diet may be due to a combination
estimated to produce a difference of about 300 kJ=d, of the greater fat loss, reduction in intra-abdominal fat
which is only about 15% of the observed difference in and to the diet composition per se. Intervention
energy balance. The greater weight loss caused by the studies comparing isoenergetic low-fat diets with
HP diet than the HC diet can therefore mainly be either high or low ratios of protein to carbohydrate
attributed to a reduction in energy intake. have demonstrated that, without changes in body
The mechanisms responsible for the high satiating weight, the exchange of protein for carbohydrate
effect of protein are not known. The energy density of reduced LDL-cholesterol and triglycerides, and
foods is an important determinant of spontaneous increased HDL-cholesterol in hypercholesterolaemic
energy intake and seems to be responsible for the subjects.37,38 The more favourable effects of the HP
higher energy intakes observed on high-fat than on diet may be only partially attributable to the larger
low-fat diets.27 However, differences in energy den- reduction in body fat.
sity are unlikely to be involved because the HP diet We did not measure blood pressure in the present
and the HC diet had similar energy densities of 4.7 ± study, but it is unlikely that dietary protein increases
5.0 kJ=g. This is in agreement with the ®nding that a blood pressure.39 Furthermore, weight loss has con-
high-protein meal suppressed hunger to a greater sistently been associated with clinically relevant
extent than two isoenergetic high-fat and high-carbo- reduction in both systolic and diastolic blood pres-
hydrate meals with the same energy density.15 The sures.40 A recent intervention study on moderately
change in daily dietary ®ber content was expectedly hypertensive patients demonstrated that a fat-reduced
lower in the HP group than in HC group, by 7 g. This diet, rich in fruits and vegetables and low-fat dairy
difference cannot explain the larger weight loss in the products, providing 18% of energy from protein,
HP group, as the higher ®ber intake would rather have reduced systolic and diastolic blood pressure by
contributed to a larger weight loss in the HC group. 5.5 mm Hg and 3.0 mm Hg more than a control
Possible differences in fat quality may have played a diet.41 This intervention resulted in a weight loss of
role, but there are no published human data to support < 0.5 kg, so there is no reason to believe that an
that differences in fat types in¯uence the satiating increase in dietary protein can offset the bene®cial
effect of the diet. Consequently, the inhibition of effect of the weight loss on blood pressure in obese
energy intake caused by the HP diet may be due to subjects.
mechanisms other than the energy density, for exam- A protein-rich diet may have other health implica-
ple, release of gut peptides, liver metabolism and a tions and its effects on osteoporosis, kidney function
direct central effect of certain amino acids.31 and colonic cancers are still a matter for debate. We
Obesity is an important risk factor of cardiovascular failed to detect any detrimental effect of the HP diet
disease (CVD) and abdominal obesity in particular is on bone mineral density and kidney size and glomer-
strongly associated with an adverse lipid pro®le, ular function (data not shown), but more studies are
ischaemic heart disease, stroke and premature needed to elucidate the contribution of high-protein
death.32 Overwhelming epidemiological data have diets to the development of these disorders. The use of
demonstrated a close association between obesity fat-reduced, high-protein diets in the treatment of
and coronary heart disease (CHD) mortality,33,34 obesity seems justi®ed because the health bene®ts of
which is attributed partly to its effects on plasma a weight loss of the magnitude observed in the present
lipid metabolism. The dyslipidaemic pro®le asso- study is associated with a marked improvement in risk
ciated with fatness and especially with excessive factors for non-insulin dependent diabetes and CVD,40Low-fat diets: High-protein vs high-carbohydrate
A Rosenvinge Skov et al
535
and possibly with a reduction in mortality.42 The meal (meat) and a high-carbohydrate meal (vegetarian) on
uncertainty about possible adverse effects means that satiety measured by automated computerized monitoring of
subsequent food intake, motivation to eat and food prefer-
the bene®cial effects observed in this treatment pro- ences. Int J Obes 1990; 14: 743 ± 751.
gram for obesity cannot yet be extrapolated to the 10 Booth DA, Chase A, Campbell AT. Relative effectiveness of
recommendation of a high-protein diet to the general protein in the late stages of appetite suppression in man.
population. Physiol Behav 1970; 5: 1299 ± 1302.
11 Astrup A, Raben A. Glucostatic control of intake and obesity.
Proc Nutr Soc 1996; 55, 485 ± 495.
12 Rolls BJ, Hetherington M, Burley VJ. The speci®city of
Conclusion satiety: the in¯uence of different macronutrient contents on
the development of satiety. Physiol Behav 1988; 43: 145 ± 153.
13 Stubbs RJ. Macronutrient effects on appetite. Int J Obes 1995;
The study shows that replacement of some dietary 19 (Suppl 5): S11 ± S19.
carbohydrate by protein in ad libitum fat-reduced 14 Hannah JS, Dubey AK, Hansen BC. Postingestional effects of
diets, for treatment of obesity, improves mean a high-protein diet on the regulation of food intake in mon-
weight loss and increases the proportion of subjects keys. Am J Clin Nutr 1990; 52: 320 ± 325.
15 Stubbs RJ, van Wyk MCW, Johnstone AM, Harbron CG.
achieving a clinically relevant weight loss. Slight Breakfasts high in protein, fat or carbohydrate: effect on
improvements in blood lipids were also observed. within-day appetite and energy balance. Eur J Clin Nutr
More freedom to choose between protein-rich and 1996; 50: 409 ± 417.
complex carbohydrate-rich foods may allow obese 16 Buemann B, Bouchard C, Tremblay A. Social class interacts
subjects to eat more lean meat and dairy products with the association between macronutrient intake and sub-
cutaneous fat. Int J Obes 1995; 19: 770 ± 775.
and hence improve adherence to low-fat diets during 17 Skov AR, Toubro S, Raben A, Astrup A. A method to achieve
weight reduction programs. control of dietary macronutrient composition in ad libitum
diets consumed by free-living subjects. Eur J Clin Nutr 1997;
51: 667 ± 672.
Acknowledgements
18 Treuth MS, Hunter GR, Kekes-Szabo T. Estimating intraab-
The study was supported by The Danish Research and dominal adipose tissue in women by dual-energy X-ray
Development Programme for Food Technology, The absorptiometry. Am J Clin Nutr 1995; 62: 527 ± 532.
Federation of Danish Pig Producers and Slaughter- 19 Kendall A, Levitsky DA, Strupp BJ, Lissner L. Weight loss on
houses, Danish Dairy Research Foundation and The a low-fat diet: consequence of the imprecision of the control
of food intake in humans. Am J Clin Nutr 1991; 53: 1124 ±
Danish Livestock and Meat Board. We also thank the 1129.
staff of Energy Metabolism and Obesity Group. 20 Raben A, Jensen NJ, Marckmann P, SandstroÈm B, Astrup A.
Finally, we thank several food producers for kindly Spontaneous weight loss during 11 weeks' ad libitum intake of
contributing to the food selection. a low fat=high ®ber diet in young, normal weight subjects. Int
J Obes 1995; 19: 916 ± 923.
21 Siggaard R, Raben A, Astrup A. Weight loss during 12 weeks'
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